We hypothesize this study will generate useful pharmacokinetic information of 4’-PPT, and we expect it will be safe and well tolerated.
ID
Bron
Verkorte titel
Aandoening
Pantothenate Kinase-Associated Neurodegeneration (PKAN)
Ondersteuning
2. Hersenstichting
3. Stichting Lepelaar will financially contribute to the study if needed.
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
1) to obtain in vivo pharmacokinetic data of 4’-PPT (the study product) measured in plasma of PKAN patients;
2) to obtain pharmacodynamic data of the biomarker COASY in circulating lymphocytes of PKAN patients, when 4’-PPT is provided daily at 3 subsequent increasing doses (7,5 mg/m2, 15 mg/m2 and 30 mg/m2) for a month each and when 4’-PPT has been orally provided over a period of 19 months on a fixed dose, based on the biomarker measurements obtained from the dose-escalation phase.
Achtergrond van het onderzoek
Background- Pantothenate kinase-associated neurodegeneration (PKAN) is an ultra-rare neurodegenerative disease affecting children and adults. Patients suffer from progressive generalized dystonia, parkinsonism and brain iron accumulation. No treatment exists for this disease. PKAN patients lack an enzyme required for biosynthesis of coenzyme A, an essential co-factor for numerous cellular metabolic reactions.
Compelling preclinical evidence shows that 4’-phosphopathetheine (4’-PPT), a downstream metabolic product of the enzyme lacking in PKAN, completely rescues the disease phenotype in PKAN animal and human cell models. Preclinical studies also identified a biomarker for a coenzyme A biosynthetic enzyme downstream from the defective enzyme in PKAN: “COASY”.
Purpose- Our study aims to collect for the first-time in vivo pharmacokinetic information of 4’-PPT, when orally administered, in PKAN patients. In addition, we will collect COASY biomarker information in relation to 4-PPT plasma concentrations. With this information, more rational dosages and dosing schedules can be designed for future 4-PPT treatment.
Methods- We perform a within-subject dose-escalation study, investigating 3 subsequent increasing doses during 5 months followed by an open label extension study of 19 months (on a fixed dose). Simultaneously we will collect information regarding safety and tolerability.
Study population- Children and adults with genetically confirmed PKAN disease. We included 10 PKAN patients in this study from the Netherlands and Belgium.
Doel van het onderzoek
We hypothesize this study will generate useful pharmacokinetic information of 4’-PPT, and we expect it will be safe and well tolerated.
Onderzoeksopzet
Patients will be visited at home 10 times during the first 5 months (M0-M4) of the dose-escalation phase. During the extension study, 1 visit after 1 year will occur and 1 visit at the end of the trial. Blood collection will occur at 10 home visits for 4’-PPT and COASY, plus routine safety laboratory tests. A standard video-recording will be taken at 6 of the visits to monitor the neurological status of the patient, and regular telephone contact will occur between the home visits as needed.
Onderzoeksproduct en/of interventie
All patients will be given 4’-PPT. Patients will be assigned a daily dose of 4’- PPT, that will be provided orally in 3 subsequent increasing doses during 5 months followed by an open label extension study of 19 months (on a fixed dose).
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Have a diagnosis of PKAN confirmed by genetic testing showing two pathogenic mutations, OR one confirmed mutation and typical clinical and imaging features of the disease.
2. Aged >12 months at the time of screening.
3. Be able to take the study product by oral route or via gastrostomy tube.
4. Informed consent is provided by the patient and/or parents and/or legal representative
5. Be resident in The Netherlands or Belgium for the duration of the trial.
6. Be in the possession of a Dutch or Belgium health insurance.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
For inclusion in this trial,
1. Subjects must NOT have been exposed to a putative PANK2 ‘bypass’ therapeutic agent in the 30 days prior to screening.
2. Subjects must NOT be concurrently enrolled in another interventional clinical trial.
3. Subjects must NOT have concurrent medical or other conditions that in the opinion of the investigators are expected to preclude completion of study procedures or confound
the assessment of clinical and laboratory measures of safety.
4. Subjects who do NOT understand Dutch.
Opzet
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL9855 |
| CCMO | NL73850.000.20 |
| OMON | NL-OMON55013 |